Leishmania are obligate intracellular protozoan parasites of macrophages that cause a spectrum of human diseases, including self-healing skin lesions, diffuse cutaneous and mucosal manifestations, and severe visceral disease. The number of cases of leishmaniasis has increased dramatically in the last 20 years, with about 2 million new cases diagnosed each year. Millions of cases of the disease now exist worldwide, primarily in Brazil, China, East Africa, India and areas of the Middle East. The disease is also endemic in the Mediterranean region, including southern France, Italy, Greece, Spain, Portugal and North Africa.
There are 20 species of Leishmania that infect humans. Of these species, Leishmania braziliensis commonly causes localized cutaneous leishmaniasis (CL). Patients with CL have strong delayed-type hypersensitivity (DTH) and in vitro proliferative responses to Leishmania antigens during both active and cured disease. Most patients with CL heal spontaneously. However, in some infected individuals, an active cutaneous disease or mucosal leishmaniasis (ML) arises, which is characterized by severe and progressive destruction of the nasal, oral and/or pharyngeal mucous membranes.
Early diagnosis of leishmaniasis may be critical for successful treatment, but is difficult to achieve since there are no distinctive signs or symptoms of the disease. Parasite detection methods have been used, but such methods are not sensitive or practical. Current serological tests (using, for example, ELISA or immunofluorescence techniques) typically use whole or lysed parasites, and are generally insensitive and prone to cross-reaction with a variety of other diseases. In addition, such methods often fail to detect the potentially fatal disease early enough to allow effective treatment, since they rely on the detection of antibodies that are present during the acute phase of the disease.
In the case of active mucosal disease, the intradermal skin test and lymphocyte proliferative responses to Leishmania antigens are exceptionally strong. In fact, it is possible that tissue destruction associated with mucosal lesions may result in part from a hypersensitivity response to Leishmania antigens. However, the specific antigens involved in the cell-mediated immune response to Leishmania have not been characterized.
Accordingly, there is a need in the art for characterization of Leishmania antigens involved in immune responses, and a determination of their role in disease manifestation. There is also a need to identify improved methods for evaluating patients in the early stages of the disease and for treating leishmaniasis. The present invention fulfills these needs and further provides other related advantages.